PROJECT SUMMARY Anxiety and depression are the two most common psychiatric conditions, affecting over a quarter of the population, and representing the leading cause of disability, worldwide. Recent meta-analyses and large-scale clinical trials suggest that only about 50% of patients improve with treatment, with substantially poorer outcomes and adherence in patients with comorbid anxiety and depression. Given the poor treatment response and adherence to currently available therapies, it is imperative to explore new ways of helping patients with anxiety and depression. Floatation-REST (Reduced Environmental Stimulation Therapy) is a relatively unexplored mind-body intervention for naturally reducing physiological stress by systematically decreasing sensory stimulation of the nervous system through the simple act of floating supine in a pool of water saturated with Epsom salt. Over the past decade floating has witnessed a rapid rise in popularity, with hundreds of recreational float centers opening across America. Despite this surge in public interest and consumption, there has been little research investigating Floatation-REST, especially in clinical populations. Our laboratory recently completed a pilot study in 30 patients with comorbid anxiety and depression showing that a single 1-hour float session was capable of inducing a large anxiolytic and antidepressant response accompanied by a substantial improvement in mood and subjective well-being. Moreover, the effects were not transient, as the subjects reported feeling sustained benefit over the next 24 hours. This proposal aims to follow-up on these promising findings by investigating the feasibility, tolerability, and safety of undergoing multiple sessions of Floatation-REST or an active comparison condition in 75 participants with clinical anxiety and depression. A subset of these participants will have the opportunity to select their preference with regard to float duration and frequency, providing important information for optimizing the ?dose? in future trials. We predict that adherence rates will be comparable across all conditions, with low dropout rates (<20%) and minimal adverse effects, providing initial evidence for feasibility, tolerability, and safety of undergoing multiple sessions of Floatation-REST and the active comparison condition in this target population. An exploratory aim examines the magnitude and duration of the anxiolytic and antidepressant effects of Floatation-REST at both short-term (up to 48 hours) and long-term (up to 6 weeks) intervals, providing an initial indication for whether any beneficial effects are sustained beyond the float experience. The results of this early phase clinical trial will help optimize the design of a future efficacy study exploring the long-term anxiolytic and antidepressant effects of Floatation-REST.